Yuen MF, Agarwal K, Gane EJ, et al. - Researchers conducted this randomised, placebo-controlled phase 1 trial to assess the pharmacokinetics, safety, and antiviral activity of ABI-H0731, an investigational inhibitor of the hepatitis B virus (HBV) core protein. This investigation was carried out in two parts. In part 1, healthy adults without hepatitis B (aged 18 to 65 years) at one clinical research centre in New Zealand (eight candidates per dose cohort) were randomly assigned (3:1) to obtain single oral doses of ABI-H0731 (100, 300, 600, or 1000 mg) or matching placebo, or once-daily or twice-daily doses of ABI-H0731 800 mg or matching placebo for seven days. In part 2, adults (aged 18 to 65 years) at clinical research centres in New Zealand, Australia, the UK, Hong Kong, Taiwan, and South Korea with chronic HBV (12 candidates per dose cohort) were randomly assigned (5:1) to obtain ABI-H0731 (100, 200, 300, or 400 mg) or matching placebo once daily for 28 days. In individuals with chronic hepatitis B, no pattern of treatment-emergent adverse events was noted at ABI-H0731 doses up to 300 mg. ABI-H0731 was quickly absorbed and showed a plasma half-life supportive of once-daily dosing. Dose-dependent decreases are consistent with the proposed mechanism of action in serum HBV DNA and RNA concentrations. Headache, influenza-like illness, rash and dizziness were the reported adverse events.